Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: Diagnosis, pathogenesis, and associated genetic markers

Diabetic neuropathy (DN) is a common long-term complication of type 1 (T1D) and type 2 (T2D) diabetes mellitus, with significant morbidity and mortality. DN is defined as impaired function of the autonomic and/or peripheral nervous system, often subclinical, particularly in children and adolescents with T1D. Nerve conduction studies (NCS) and skin biopsies are considered gold-standard methods in the assessment of DN. Multiple environmental and genetic factors are involved in the pathogenesis of DN. Specifically, the role of metabolic control and glycemic variability is of paramount importance. A number of recently identified genes, including the AKR1B1, VEGF, MTHFR, APOE, and ACE genes, contribute significantly in the pathogenesis of DN. These genes may serve as biomarkers to predict future DN development or treatment response. In addition, they may serve as the basis for the development of new medications or gene therapy. In this review, the diagnostic evaluation, pathogenesis, and associated genetic markers of DN in children and adolescents with T1D are presented and discussed.